SSADHD
MCID: SCC001
MIFTS: 53

Succinic Semialdehyde Dehydrogenase Deficiency (SSADHD) malady

Categories: Genetic diseases, Rare diseases, Neuronal diseases, Metabolic diseases

Aliases & Classifications for Succinic Semialdehyde Dehydrogenase Deficiency

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Aliases & Descriptions for Succinic Semialdehyde Dehydrogenase Deficiency:

Name: Succinic Semialdehyde Dehydrogenase Deficiency 52 11 23 48 24 25 54 70 12 13 68
4-Hydroxybutyric Aciduria 11 23 48 24 25 54 70
Gamma-Hydroxybutyric Aciduria 11 23 24 25 54 70
Ssadh Deficiency 23 48 24 25 54 70
Succinate Semialdehyde Dehydrogenase Deficiency 70 27
Gaba Metabolic Defect 48 70
 
Succinic Semialdehyde Dehydrogenase 12
Gamma-Hydroxybutyric Acidemia 25
Gamma-Hydroxybutyricaciduria 48
4-Hydroxybutyricaciduria 25
Ssadhd 70
Ssadh 11

Characteristics:

Orphanet epidemiological data:

54
succinic semialdehyde dehydrogenase deficiency:
Inheritance: Autosomal recessive; Age of onset: Childhood,Infancy,Neonatal; Age of death: adult

HPO:

64
succinic semialdehyde dehydrogenase deficiency:
Inheritance: autosomal recessive inheritance
Onset and clinical course: infantile onset, phenotypic variability

Classifications:



External Ids:

OMIM52 271980
Disease Ontology11 DOID:0060175
Orphanet54 ORPHA22
ICD10 via Orphanet31 E72.8
MedGen37 C0268631
MeSH39 D000592

Summaries for Succinic Semialdehyde Dehydrogenase Deficiency

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Genetics Home Reference:25 Succinic semialdehyde dehydrogenase deficiency is a disorder that can cause a variety of neurological problems. People with this condition typically have developmental delay, especially involving speech development; intellectual disability; and decreased muscle tone (hypotonia) soon after birth. About half of those affected experience seizures, difficulty coordinating movements (ataxia), decreased reflexes (hyporeflexia), and behavioral problems. The most common behavioral problems associated with this condition are sleep disturbances, hyperactivity, difficulty maintaining attention, and anxiety. Less frequently, affected individuals may have increased aggression, hallucinations, obsessive-compulsive disorder (OCD), and self-injurious behavior, including biting and head banging. People with this condition can also have problems controlling eye movements. Less common features of succinic semialdehyde dehydrogenase deficiency include uncontrollable movements of the limbs (choreoathetosis), involuntary tensing of the muscles (dystonia), muscle twitches (myoclonus), and a progressive worsening of ataxia.

MalaCards based summary: Succinic Semialdehyde Dehydrogenase Deficiency, also known as 4-hydroxybutyric aciduria, is related to epilepsy and hypotonia, and has symptoms including ataxia, ataxia and seizures. An important gene associated with Succinic Semialdehyde Dehydrogenase Deficiency is ALDH5A1 (Aldehyde Dehydrogenase 5 Family Member A1), and among its related pathways are Valproic Acid Pathway, Pharmacodynamics and Cyclophosphamide Pathway, Pharmacodynamics. Affiliated tissues include eye, globus pallidus and brain.

Disease Ontology:11 A gamma-amino butyric acid metabolism disorder that is characterized by a deficiency of succinic semialdehyde dehydrogenase resulting in elevated levels of gamma-hydroxybutyric acid.

NIH Rare Diseases:48 Succinic semialdehyde dehydrogenase (ssadh) deficiency is disorder that can cause a variety of neurological and neuromuscular problems. the signs and symptoms can be extremely variable among affected individuals and may include mild to severe intellectual disability; developmental delay (especially involving speech); hypotonia; difficulty coordinating movements (ataxia); and/or seizures. some affected individuals may also have decreased reflexes (hyporeflexia); nystagmus; hyperactivity; and/or behavioral problems. ssadh deficiency is caused by mutations in the aldh5a1 gene and is inherited in an autosomal recessive manner. management is generally symptomatic and typically focuses on treating seizures and neurobehavioral issues. last updated: 9/25/2013

OMIM:52 Succinic semialdehyde dehydrogenase deficiency (SSADHD) is a rare autosomal recessive neurologic disorder in which an... (271980) more...

UniProtKB/Swiss-Prot:70 Succinic semialdehyde dehydrogenase deficiency: A rare inborn error of 4-aminobutyric acid (GABA) metabolism, which leads to accumulation of 4-hydroxybutyric acid in physiologic fluids of patients. The disease is clinically characterized by developmental delay, hypotonia, mental retardation, ataxia, seizures, hyperkinetic behavior, aggression, and sleep disturbances.

Wikipedia:71 Succinic semialdehyde dehydrogenase deficiency (SSADHD), also known as 4-hydroxybutyric aciduria or... more...

GeneReviews for NBK1195

Related Diseases for Succinic Semialdehyde Dehydrogenase Deficiency

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Graphical network of diseases related to Succinic Semialdehyde Dehydrogenase Deficiency:



Diseases related to succinic semialdehyde dehydrogenase deficiency

Symptoms & Phenotypes for Succinic Semialdehyde Dehydrogenase Deficiency

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Symptoms by clinical synopsis from OMIM:

271980

Clinical features from OMIM:

271980

Human phenotypes related to Succinic Semialdehyde Dehydrogenase Deficiency:

 54 64 (show all 23)
id Description HPO Frequency Orphanet Frequency HPO Source Accession
1 behavioral abnormality64 54 Frequent (79-30%) HP:0000708
2 intellectual disability64 54 Very frequent (99-80%) HP:0001249
3 ataxia64 54 Very frequent (99-80%) HP:0001251
4 muscular hypotonia64 54 Very frequent (99-80%) HP:0001252
5 global developmental delay64 54 Very frequent (99-80%) HP:0001263
6 abnormality of metabolism/homeostasis64 54 Very frequent (99-80%) HP:0001939
7 generalized tonic-clonic seizures64 54 Frequent (79-30%) HP:0002069
8 generalized myoclonic seizures64 54 Frequent (79-30%) HP:0002123
9 status epilepticus64 54 Frequent (79-30%) HP:0002133
10 abnormality of eye movement64 HP:0000496
11 psychosis64 HP:0000709
12 autism64 HP:0000717
13 aggressive behavior64 HP:0000718
14 hallucinations64 HP:0000738
15 anxiety64 HP:0000739
16 delayed speech and language development64 HP:0000750
17 hyperactivity64 HP:0000752
18 hyporeflexia64 HP:0001265
19 motor delay64 HP:0001270
20 absence seizures64 HP:0002121
21 eeg abnormality64 HP:0002353
22 hyperkinesis64 HP:0002487
23 self-injurious behavior64 HP:0100716

UMLS symptoms related to Succinic Semialdehyde Dehydrogenase Deficiency:


ataxia, seizures

Drugs & Therapeutics for Succinic Semialdehyde Dehydrogenase Deficiency

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Drugs for Succinic Semialdehyde Dehydrogenase Deficiency (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 6)
idNameStatusPhaseClinical TrialsCas NumberPubChem Id
1Protective AgentsPhase 27443
2Neurotransmitter AgentsPhase 218340
3Neuroprotective AgentsPhase 21716
4(3-aminopropyl)(n-butyl)phosphinic acidPhase 22
5GABA AgentsPhase 21684
6
Taurineexperimental, Nutraceutical28107-35-71123
Synonyms:
1-Aminoethane-2-sulfonate
1-Aminoethane-2-sulfonic acid
2-Aminoethanesulfonate
2-Aminoethanesulfonic acid
2-Aminoethylsulfonate
2-Aminoethylsulfonic acid
 
2-Sulfoethylamine
Aminoethylsulfonate
Aminoethylsulfonic acid
Taurine
b-Aminoethylsulfonate
b-Aminoethylsulfonic acid
beta-Aminoethylsulfonate
beta-Aminoethylsulfonic acid

Interventional clinical trials:

idNameStatusNCT IDPhase
1Phase 2 Clinical Trial of SGS-742 Therapy in Succinic Semialdehyde Dehydrogenase DeficiencyRecruitingNCT02019667Phase 2
2PET Imaging of GABA Receptors in Succinic Semialdehyde Dehydrogenase DeficiencyCompletedNCT00246870
3Brain Excitability in Patients With Succinic Semialdehyde Dehydrogenase DeficiencyCompletedNCT00132366
4Taurine Therapy for SSADH DeficiencyCompletedNCT01608178

Search NIH Clinical Center for Succinic Semialdehyde Dehydrogenase Deficiency

Genetic Tests for Succinic Semialdehyde Dehydrogenase Deficiency

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Genetic tests related to Succinic Semialdehyde Dehydrogenase Deficiency:

id Genetic test Affiliating Genes
1 Succinate-Semialdehyde Dehydrogenase Deficiency27
2 Succinic Semialdehyde Dehydrogenase Deficiency24 ALDH5A1

Anatomical Context for Succinic Semialdehyde Dehydrogenase Deficiency

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MalaCards organs/tissues related to Succinic Semialdehyde Dehydrogenase Deficiency:

36
Eye, Globus pallidus, Brain, Liver

Publications for Succinic Semialdehyde Dehydrogenase Deficiency

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Articles related to Succinic Semialdehyde Dehydrogenase Deficiency:

(show top 50)    (show all 78)
idTitleAuthorsYear
1
Gamma-Hydroxybutyrate (GHB) Content in Hair Samples Correlates Negatively with Age in Succinic Semialdehyde Dehydrogenase Deficiency. (28213850)
2017
2
Succinic Semialdehyde Dehydrogenase Deficiency Presenting as Autism Spectrum Disorder. (26806207)
2016
3
Psychomotor delay, hypotonia, and behavioural disorders: A case of succinic semialdehyde dehydrogenase deficiency. (26964512)
2016
4
Succinic semialdehyde dehydrogenase deficiency (SSADHD): Pathophysiological complexity and multifactorial trait associations in a rare monogenic disorder of GABA metabolism. (27311541)
2016
5
Eye Findings on Vigabatrin and Taurine Treatment in Two Patients with Succinic Semialdehyde Dehydrogenase Deficiency. (27104484)
2016
6
Acute Infantile Encephalopathy as Presentation of Succinic Semialdehyde Dehydrogenase Deficiency. (27268762)
2016
7
Biomarkers in a Taurine Trial for Succinic Semialdehyde Dehydrogenase Deficiency. (27338723)
2016
8
A case of succinic semialdehyde dehydrogenase deficiency with status epilepticus and rapid regression. (27117035)
2016
9
Correlation of blood biomarkers with age informs pathomechanisms in succinic semialdehyde dehydrogenase deficiency (SSADHD), a disorder of GABA metabolism. (27686230)
2016
10
Succinic semialdehyde dehydrogenase deficiency of four Chinese patients and prenatal diagnosis for three fetuses. (26220405)
2015
11
Natural history of succinic semialdehyde dehydrogenase deficiency through adulthood. (26268900)
2015
12
A case of acute onset succinic semialdehyde dehydrogenase deficiency: neuroimaging findings and literature review. (26499347)
2015
13
Taurine trial in succinic semialdehyde dehydrogenase deficiency and elevated CNS GABA. (24523482)
2014
14
Evidence of redox imbalance in a patient with succinic semialdehyde dehydrogenase deficiency. (27896081)
2014
15
Succinic Semialdehyde Dehydrogenase Deficiency in a Chinese Boy: A Novel ALDH5A1 Mutation With Severe Phenotype. (25122112)
2014
16
A Novel Mutation of ALDH5A1 Gene Associated With Succinic Semialdehyde Dehydrogenase Deficiency. (25246302)
2014
17
Analysis of ALDH5A1 gene mutation in a Chinese Han family with succinic semialdehyde dehydrogenase deficiency]. (23926001)
2013
18
Thirty years beyond discovery--clinical trials in succinic semialdehyde dehydrogenase deficiency, a disorder of GABA metabolism. (22739941)
2013
19
Therapeutic efficacy of magnesium valproate in succinic semialdehyde dehydrogenase deficiency. (23430529)
2013
20
A novel ALDH5A1 mutation is associated with succinic semialdehyde dehydrogenase deficiency and severe intellectual disability in an Iranian family. (23825041)
2013
21
Succinic semialdehyde dehydrogenase deficiency: an inheritable neurometabolic disease]. (23516105)
2013
22
A boy with a severe phenotype of succinic semialdehyde dehydrogenase deficiency. (21612881)
2012
23
Efficacy of vigabatrin intervention in a mild phenotypic expression of succinic semialdehyde dehydrogenase deficiency. (23430864)
2012
24
A novel ALDH5A1 mutation in a patient with succinic semialdehyde dehydrogenase deficiency. (22437753)
2012
25
Epilepsy in succinic semialdehyde dehydrogenase deficiency, a disorder of GABA metabolism. (21664777)
2011
26
Head bobbing due to succinic semialdehyde dehydrogenase deficiency. (20548048)
2010
27
Cerebellar atrophy in human and murine succinic semialdehyde dehydrogenase deficiency. (20445195)
2010
28
Neuropathology in succinic semialdehyde dehydrogenase deficiency. (20304328)
2010
29
Succinic semialdehyde dehydrogenase deficiency: decrease in 4-OH-butyric acid levels with low doses of vigabatrin]. (20018576)
2010
30
Sleep disorders in succinic semialdehyde dehydrogenase deficiency: a family report. (19896403)
2010
31
Succinic semialdehyde dehydrogenase deficiency: lessons from mice and men. (19172412)
2009
32
Decreased GABA-A binding on FMZ-PET in succinic semialdehyde dehydrogenase deficiency. (19667317)
2009
33
Circadian distribution of generalized tonic-clonic seizures associated with murine succinic semialdehyde dehydrogenase deficiency, a disorder of GABA metabolism. (18514581)
2008
34
Neuropsychiatric morbidity in adolescent and adult succinic semialdehyde dehydrogenase deficiency patients. (18622364)
2008
35
'Succinic semialdehyde dehydrogenase deficiency: phenotype evolution in an adolescent patient at 20-year follow-up'. (18811705)
2008
36
Evidence for oxidative stress in tissues derived from succinate semialdehyde dehydrogenase-deficient mice. (17885820)
2007
37
Enzymatic and metabolic evidence for a region specific mitochondrial dysfunction in brains of murine succinic semialdehyde dehydrogenase deficiency (Aldh5a1-/- mice). (17303287)
2007
38
Vigabatrin improves paroxysmal dystonia in succinic semialdehyde dehydrogenase deficiency. (17438226)
2007
39
Succinic semialdehyde dehydrogenase deficiency: clinical, biochemical and molecular characterization of a new patient with severe phenotype and a novel mutation. (16542398)
2006
40
Clinical, cytogenetic and molecular characterization of a patient with combined succinic semialdehyde dehydrogenase deficiency and incomplete WAGR syndrome with obesity. (16545979)
2006
41
Succinic semialdehyde dehydrogenase deficiency: GABAB receptor-mediated function. (16647690)
2006
42
Proton MR spectroscopy in succinic semialdehyde dehydrogenase deficiency. (15037717)
2004
43
Succinic semialdehyde dehydrogenase deficiency (SSADH) (4-hydroxybutyric aciduria, gamma-hydroxybutyric aciduria). (15341910)
2004
44
Mental retardation and hypotonia seen in the knock out mouse for Canavan disease is not due to succinate semialdehyde dehydrogenase deficiency. (15016427)
2004
45
Liver-directed adenoviral gene transfer in murine succinate semialdehyde dehydrogenase deficiency. (15093183)
2004
46
Absence seizures in succinic semialdehyde dehydrogenase deficient mice: a model of juvenile absence epilepsy. (15582027)
2004
47
The molecular basis of succinic semialdehyde dehydrogenase deficiency in one family. (15059623)
2004
48
Neurodevelopmental pattern of succinic semialdehyde dehydrogenase deficiency (gamma-hydroxybutyric aciduria). (15287248)
2004
49
Succinic semialdehyde dehydrogenase deficiency in children and adults. (12891657)
2003
50
Effect of valproic acid on the urinary metabolic profile of a patient with succinic semialdehyde dehydrogenase deficiency. (12829002)
2003

Variations for Succinic Semialdehyde Dehydrogenase Deficiency

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UniProtKB/Swiss-Prot genetic disease variations for Succinic Semialdehyde Dehydrogenase Deficiency:

70 (show all 12)
id Symbol AA change Variation ID SNP ID
1ALDH5A1p.Cys93PheVAR_026199rs765561257
2ALDH5A1p.Gly176ArgVAR_026200rs72552281
3ALDH5A1p.Cys223TyrVAR_026201rs72552282
4ALDH5A1p.Thr233MetVAR_026202
5ALDH5A1p.Asn255SerVAR_026203rs145087265
6ALDH5A1p.Gly268GluVAR_026204rs375628463
7ALDH5A1p.Asn335LysVAR_026205rs72552283
8ALDH5A1p.Pro382LeuVAR_026206
9ALDH5A1p.Pro382GlnVAR_026207
10ALDH5A1p.Gly409AspVAR_026208rs118203984
11ALDH5A1p.Val487GluVAR_026209
12ALDH5A1p.Gly533ArgVAR_026210rs72552284

Clinvar genetic disease variations for Succinic Semialdehyde Dehydrogenase Deficiency:

5
id Gene Variation Type Significance SNP ID Assembly Location
1ALDH5A1ALDH5A1, IVS9, G-T, +1SNVPathogenic
2ALDH5A1ALDH5A1, IVS5, G-A, +1SNVPathogenic
3ALDH5A1NM_ 170740.1(ALDH5A1): c.612G> A (p.Trp204Ter)SNVPathogenicrs118203982GRCh37Chr 6, 24505099: 24505099
4ALDH5A1NM_ 170740.1(ALDH5A1): c.1273C> T (p.Arg425Ter)SNVPathogenicrs118203983GRCh37Chr 6, 24528285: 24528285
5ALDH5A1NM_ 001080.3(ALDH5A1): c.1226G> A (p.Gly409Asp)SNVPathogenicrs118203984GRCh37Chr 6, 24528277: 24528277
6ALDH5A1NG_ 008161.1: g.31299_ 33753del2455deletionPathogenicGRCh37Chr 6, 24521495: 24523949
7ALDH5A1NM_ 170740.1(ALDH5A1): c.1382+1_ 1382+3delinsTTindelPathogenicrs875989801GRCh37Chr 6, 24528395: 24528397

Expression for genes affiliated with Succinic Semialdehyde Dehydrogenase Deficiency

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Search GEO for disease gene expression data for Succinic Semialdehyde Dehydrogenase Deficiency.

Pathways for genes affiliated with Succinic Semialdehyde Dehydrogenase Deficiency

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Pathways related to Succinic Semialdehyde Dehydrogenase Deficiency according to GeneCards Suite gene sharing:

(show all 21)
idSuper pathwaysScoreTop Affiliating Genes
1
Show member pathways
9.8ABAT, ALDH5A1
2
Show member pathways
9.6ALDH2, ALDH5A1
39.6ABAT, ALDH6A1
4
Show member pathways
9.5ABAT, GAD1
5
Show member pathways
9.5ABAT, GAD1
6
Show member pathways
9.2ABAT, ALDH5A1, GAD1
7
Show member pathways
9.2ABAT, ALDH5A1, GAD1
88.8ABAT, ALDH4A1, ALDH5A1, GAD1
9
Show member pathways
8.7ALDH1B1, ALDH2, ALDH3A2
10
Show member pathways
8.7ALDH1B1, ALDH2, ALDH3A2
11
Show member pathways
8.7ALDH1B1, ALDH2, ALDH3A2
12
Show member pathways
8.7ALDH1B1, ALDH2, ALDH3A2
138.7ALDH1B1, ALDH2, ALDH3A2
14
Show member pathways
8.7ALDH1B1, ALDH2, ALDH3A2
15
Show member pathways
8.7ALDH1B1, ALDH2, ALDH3A2
16
Show member pathways
8.7ALDH1B1, ALDH2, ALDH3A2
17
Show member pathways
8.7ABAT, ALDH2, ALDH5A1, GAD1
18
Show member pathways
8.3ALDH1B1, ALDH2, ALDH3A2, ALDH4A1
19
Show member pathways
7.8ABAT, ALDH1B1, ALDH2, ALDH3A2, ALDH6A1
20
Show member pathways
7.2ABAT, ALDH1B1, ALDH2, ALDH3A2, ALDH6A1, GAD1
21
Show member pathways
6.1ABAT, AKR7A2, ALDH1B1, ALDH2, ALDH3A2, ALDH4A1

GO Terms for genes affiliated with Succinic Semialdehyde Dehydrogenase Deficiency

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Cellular components related to Succinic Semialdehyde Dehydrogenase Deficiency according to GeneCards Suite gene sharing:

idNameGO IDScoreTop Affiliating Genes
1mitochondrial matrixGO:00057598.7ABAT, ALDH1B1, ALDH2, ALDH4A1, ALDH5A1, ALDH6A1
2mitochondrionGO:00057396.5ABAT, ALDH1B1, ALDH2, ALDH3A2, ALDH4A1, ALDH5A1

Biological processes related to Succinic Semialdehyde Dehydrogenase Deficiency according to GeneCards Suite gene sharing:

(show all 10)
idNameGO IDScoreTop Affiliating Genes
1gamma-aminobutyric acid catabolic processGO:000945010.5ABAT, ALDH5A1
2gamma-aminobutyric acid metabolic processGO:000944810.5ABAT, ALDH5A1
3neurotransmitter catabolic processGO:004213510.5ABAT, ALDH5A1
4gamma-aminobutyric acid biosynthetic processGO:000944910.2ABAT, GAD1
5ethanol catabolic processGO:000606810.2ALDH1B1, ALDH2
6ethanol oxidationGO:000606910.2ALDH1B1, ALDH2
7cellular aldehyde metabolic processGO:000608110.0AKR7A2, ALDH3A2
8carbohydrate metabolic processGO:00059759.8AKR7A2, ALDH1B1, ALDH2
9metabolic processGO:00081528.1ALDH1B1, ALDH2, ALDH3A2, ALDH4A1, ALDH5A1, ALDH6A1
10oxidation-reduction processGO:00551147.0AKR7A2, ALDH1B1, ALDH2, ALDH3A2, ALDH4A1, ALDH5A1

Molecular functions related to Succinic Semialdehyde Dehydrogenase Deficiency according to GeneCards Suite gene sharing:

(show all 7)
idNameGO IDScoreTop Affiliating Genes
1NAD bindingGO:005128710.2ALDH1B1, ALDH2
2electron carrier activityGO:00090559.8AKR7A2, ALDH2, ALDH4A1
3aldehyde dehydrogenase [NAD(P)+] activityGO:00040309.8ALDH2, ALDH3A2
4pyridoxal phosphate bindingGO:00301709.5ABAT, GAD1
5aldehyde dehydrogenase (NAD) activityGO:00040299.0ALDH1B1, ALDH2, ALDH3A2, ALDH4A1
6oxidoreductase activity, acting on the aldehyde or oxo group of donors, NAD or NADP as acceptorGO:00166207.9ALDH1B1, ALDH2, ALDH3A2, ALDH4A1, ALDH5A1, ALDH6A1
7oxidoreductase activityGO:00164917.5AKR7A2, ALDH1B1, ALDH2, ALDH3A2, ALDH4A1, ALDH5A1

Sources for Succinic Semialdehyde Dehydrogenase Deficiency

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2CDC
6CNVD
10DGIdb
15ExPASy
16FDA
17FMA
27GTR
28HGMD
29HMDB
30ICD10
31ICD10 via Orphanet
32ICD9CM
33IUPHAR
34KEGG
37MedGen
39MeSH
40MESH via Orphanet
41MGI
44NCI
45NCIt
46NDF-RT
49NINDS
50Novoseek
52OMIM
53OMIM via Orphanet
57PubMed
58QIAGEN
63SNOMED-CT via Orphanet
67Tumor Gene Family of Databases
68UMLS
69UMLS via Orphanet